The aim of this grant proposal is to support a set of core facilities that spreads understanding and use of new technologies to the wide range of neuroscientists in our community. The scientific cores are: (1) Light Microscopy, which enables neuroscientists to visualize neural circuit structure and function with great specificity and resolution using the newest super-resolution fluorescence microscopy, multiphoton, and confocal instruments; (2) Electron Microscopy, with TEM and a new high-throughput, serial scanning EM; and (3) Neuroengineering, which provides design and fabrication expertise to allow individual users to adapt the latest electronic, imaging, and computer technologies for their experiments. Two additional facilities, devoted to Neuroimaging (including human brain and small animal scanners) and Genome Modification (providing transgenic and targeted mutant mice for structural or functional analysis), are supported from other sources, but will be integrated with the three Cores supported here, providing neuroscientists with access to the full range of imaging modalities currently driving the field forward. An Administrative Core tracks the usage and finances of the scientific cores, oversees coordination among all cores, and facilitates interactions between the core users and core technical staff. Individuals will find equipment and services in these Cores that are difficult or impossible to support in individual labs, which lack sufficient technical expertise, money, and space. The users, members of Harvard's Cambridge-based neuroscience community, will be drawn closer together, through shared space, equipment, and techniques. We also understand that many of these newer technologies are difficult to understand and implement, and so they are not utilized as broadly as might be wished. Thus we propose not only to establish these Cores but also to adopt multiple strategies aimed at reducing barriers to their widespread utilization. These include formal and informal education, making most core services available without user fees, and providing ample technical support. Our ambitious model has begun to shift the paradigm for neuroscience research from complete reliance on individual laboratory-centered facilities to the more cost-effective and productive use of extraordinary shared facilities.